PROJECT SUMMARY This project will describe the differing epidemiological and ecological patterns of cholera in two ?hotspot? regions near the great lakes of Tanzania and Cameroon to understand the nature of cholera emergence and transmission in these areas of Africa. Our group has described cholera?s epidemiology and ecology in Bangladesh where cholera follows a predictable annual schedule. V. cholerae, both culturable and non-culturable forms can be detected in the ponds of Bangladesh, suggesting that vibrios from environmental reservoirs directly infect humans, leading to fecal-oral transmission and seasonal outbreaks. The seasonality in Bangladesh indicates climatic factors to be a major determinant for initiating and / or accelerating these outbreaks. In contrast to this consistent pattern in Bangladesh, African cholera outbreaks are much less predictable and they differ between countries. Cholera ?hotspots? occur around the great lakes of Tanzania and Cameroon. For example, in Cameroon, severe outbreaks occur every few years with high case fatality rates, but cases are not detected during intervening lean periods. Similarly, Tanzania has outbreaks sporadically. Working with the Tanzanian Health Ministry, using molecular methods from recent outbreaks, we could differentiate localized outbreaks from other more widely disseminated outbreaks which were associated with continued spread. Similarly, in Cameroon, an outbreak in one region could be traced as it moved to the Lake Chad region. The study will conduct clinical and environmental surveillance for culturable and non-culturable V. cholerae in two regions of Tanzania (Dar es Salaam and surrounding areas and rural Kigoma) and the Far North Region of Cameroon. We will characterize the V. cholerae isolates and lytic vibriophage from cholera patients seeking care at hospital as well as community contacts to compare strains from index cases with those from nearby water sources and neighbors. These will also be compared to strains from other areas in Africa. Ecological surveillance will be used to associate transmission with the presence of lytic vibriophage, weather patterns; and water characteristics. Thus, this proposal will describe the molecular epidemiology and ecology of cholera in Tanzania and Cameroon to improve our understanding of transmission patterns of cholera across large areas of Africa, including factors that limit transmission. The research will evaluate outbreaks in which cholera emerges as a localized outbreak with limited transmission, or alternatively, results from widely transmitted introductions across borders. By providing a more complete understanding of factors, including vibriophage, leading to cholera?s emergence into epidemics, as well as their collapse, the project will guide the development of interventions to control cholera in Africa.